Inflammasome Activation in Bovine Peripheral Blood-Derived Macrophages Is Associated with Actin Rearrangement.

Amin Tahoun,Amira M Rizk,Kirsty Jensen,David Gally,Hanem El-Sharkawy,Jamaan Ajarem,Ahmed Allam,Ayman M Mahmoud

doi:10.3390/ani10040655

Abstract

Simple SummaryIn the early stage of infection, the innate immune system produces a rapid inflammatory response that blocks the growth and spread of the infectious agent. In this study, we explored the role of the actin cellular cytoskeleton in the inflammatory response due to stimulation of the bovine macrophages with Salmonella typhimurium flagellin. We found that actin was rearranged to form filopodia, which in the early stage of inflammation are important for macrophage motility. As inflammation progressed, actin polymerized at the same site as inflammasome complexes formed. Ultimately the macrophage died, which will attract more inflammatory cells to the infection site to help block the infection. Inflammation is critical for infection control and acts as an arsenal defense mechanism against invading microbes through activation of the host immune system. It works via its inflammasome components to sense the dangerous invading microorganism and send messages to the immune system to destroy them. To date, the function of bovine macrophage inflammasome and its relationship with actin has not been identified. This study aimed to investigate the activation of bovine inflammasome by phase one flagellin from Salmonella typhimurium and its interaction with actin. Bovine monocyte-derived macrophages were prepared and challenged with S. typhimurium SL1344 phase one flagellin. The results demonstrated the relationship between the flagellin-based activation of inflammasome and actin rearrangement. The flagellin-based activation of inflammasome promoted the activation and co-localization of F-actin and the inflammasome complex. Actin was remodeled to different degrees according to the stage of inflammasome activation. The actin redistribution varied from polymerization to filopodia, while at the stage of pyroptotic cell death, actin was broken down and interacted with activated inflammasome complexes. In conclusion, flagellin-dependent inflammasome activation and actin localization to the inflammasome at the stage of pyroptotic cell death may be of importance for appropriate immune responses, pending further studies to explore the exact cross-linking between the inflammasome complex and actin.

Highlights

Macrophages have complex functions in the immune system, playing an essential role in both innate and adaptive immunity [1,2]
We have previously shown that bovine macrophages detect Escherichia coli flagellin [33], which resulted in the production of we have recently shown that bovine macrophages detect flagellin from other bacteria [46], whereas the stimulation with extracellular E. coli flagellin did not result in the production of active IL-1β
Our results have provided new and unequivocal evidence that actin inflammasome interaction in response to flagellin is an important part of the inflammation process

Summary

Introduction

Macrophages have complex functions in the immune system, playing an essential role in both innate and adaptive immunity [1,2]. Their role in innate immunity as phagocytic cells is a very crucial part of the host defense system [3]. The macrophages’ recognition of different pathogens is conferred by multiple specialized cellular receptors that induce cellular signals to activate the immune system. These receptors include the pattern recognition receptors (PRR) of which the Nod-like receptors (NLRs) and Toll-like receptors (TLRs) are important to sense the pathogen associated molecular patterns (PAMP) of various micro-organisms [4]. One of the most important weapons of the macrophage arsenal is the activation of TLRs and inflammasomes that activate the host innate responses [8]

Objectives

Methods

Results

Discussion

Conclusion